The verbal fluency (VF) test is associated with prefrontal and cingulate functioning. We used positron emission tomography (PET) to test the hypothesis that inactivity in these regions can explain why patients with depression often perform poorly on this test. Forty-one patients with major depression and 46 controls were scanned during rest and during activation with the VF test. The differences between the two conditions were mapped for each of the two groups, and between-group differences in the activation pattern were calculated on a voxel-by-voxel basis. As predicted, the patients performed significantly more poorly on the test. In both groups activations were seen in the left anterior cingulate region, the left dorsolateral prefrontal cortex, the left medial prefrontal cortex, and the right cerebellum. Performance was correlated to the cerebral perfusion in to the left occipitotemporal gyrus and the left cerebellum. However, no difference in activation between the two groups was significant. The present study had sufficient power to detect potential differences between the two groups, and the subtraction tasks were appropriate. Therefore, the result supports the notion that abnormalities in the prefrontal cortex in depression are qualitative in nature rather than quantitative; this suggests depression involves dys-coordination of neural activity in the frontal lobes rather than a simple reduction in activity.